Structure and mechanism of the ECF-type ABC transporter for thiamin

PhD ceremony: Mr. G.B. Erkens, 14.45 uur, Doopsgezinde Kerk, Oude Boteringestraat 33, Groningen

Dissertation: Structure and mechanism of the ECF-type ABC transporter for thiamin

Promotor(s): prof. D.J. Slotboom

Faculty: Mathematics and Natural Sciences

Guus Erkens’ PhD thesis is about the thiamin (vitamin B1) transport protein ThiT from the bacterium Lactococcus lactis. During his research project he has investigated the recognition of thiamin by ThiT. Also he has determined the three-dimensional structure of ThiT using X-ray crystallography. These results may provide a starting point for the development of new antibiotics.

The uptake of vitamins requires specific transport proteins residing in the cell membrane. Studying membrane proteins is notoriously difficult. Our knowledge of these protein mechanisms is therefore limited. Alike humans and other organisms bacteria depend on vitamins for their survival. Many bacteria are capable of producing vitamins but often depend on the uptake of vitamins from their environment as well.

The determination of the three-dimensional structure of a membrane protein is technically very challenging. Therefore very few membrane protein structures are available. The results presented by Erkens have yielded great insight in the mechanism of ThiT and in vitamin transport in general. Proteins are constructed of long chains folded in a complex three-dimensional pattern. Their function is largely determined by this pattern.

In co-operation with other researchers more vitamin transport proteins similar to ThiT have been identified. These findings have lead to a more detailed biochemical study of ThiT. After purifying the protein from Lactococcus lactis cell membranes, the interaction of ThiT with thiamin could be investigated. Thiamin binding to ThiT turned out to be of a very high affinity. Given these results Erkens concluded that high affinity binding allows bacteria to take up thiamin when it is available in very low concentrations.

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